The central goal of this proposal is to develop reagents and strategies to support low cost, high volume genotyping efforts for both mouse and human genetics. The principle which underlies our approach is the use of PCR based methods which reproducibly yield a set of hundreds to thousands of single copy genomic fragments distributed across the genetic map. Genetic markers based on single nucleotide polymorphisms (SNPs) identified in such sets of genomic sequences can be genotyped in a simple hybridization based format at low cost with high efficiency and accuracy. Interspersed repetitive sequence polymerase chain reaction (IRS PCR) is a methodology we have explored and developed during the previous granting period to achieve this objective. In the mouse, we have utilized this methodology in pilot studies to identify SNP markers among common inbred strains which can be genotyped using a simple high throughput allele specific oligonucleotide (ASO) procedure. We have also carried out parallel studies which support the feasibility of this approach for human genotyping. In the current application we propose to scale up the current marker generation program to build a collection of genetic markers which can support a low cost, high throughput genotyping effort for both mouse and human genetics. One set of specific aims is directly focused on the process of SNP marker generation and characterization based on processes which have already been developed at pilot scale. A second group of specific aims is focused on technical development efforts to support the central goal of the program.